We used capture-recapture methodology to estimate total deaths and efficiency of reporting for 2 systems. During 1987-1992, there were 165 measles-associated deaths in the multiple-cause mortality database at the National Center for Health Statistics (NCHS) and 184 reported to the measles surveillance system at the National Immunization Program (NIP). We estimated that 259 measles deaths actually occurred; the reporting efficiencies were 64% for the NCHS and 71% for the NIP. Overall the death-to-case ratio was 2.54 and 2.83 deaths/1000 reported cases, using the NCHS and NIP data, respectively. Pneumonia was a complication among 67% of measles-related deaths in the NCHS data and 86% of deaths in the NIP data. Encephalitis was reported in 11% of deaths in both databases. Preexisting conditions related to immune deficiency were reported for 16% of deaths in the NCHS system and 14% in the NIP; the most common was human immunodeficiency virus infection. Overall, 90% of deaths reported to the NIP occurred in persons who had not been vaccinated against measles. During 1993-1999, only 1 acute measles-related death was reported to the NCHS and no deaths were reported to the NIP. This is consistent with the extremely low reported incidence of measles in the United States during these years.

Vaccination at 6 months of age followed by routine revaccination is recommended when exposure of infants to measles is likely. Dade County, Florida, began this early two-dose schedule during a large epidemic in 1986-1987 (i.e., 22% of cases occurred in infants aged 6-11 months). This schedule was continued routinely in high-risk areas. The effect of an early two-dose schedule on measles prevention in the county was examined by comparing measles vaccination coverage and epidemiology before (1985-1987) and after (1988-1996) the schedule became routine. To assess serologic response, seroprevalence of measles antibody among children aged 4-6 years in 1995 was examined. To evaluate vaccine effectiveness, a case-control study was conducted among preschool-aged children. Among those aged 2 years, vaccination coverage with > or =1 dose increased from 75% to 94% in 1996. The number of annual cases declined, and endemic measles transmission reportedly ended after 1993. Seroprevalence of plaque reduction neutralization antibody (titer > 1:120) among those receiving vaccination according to an early two-dose schedule and a single dose at age > or =12 months was 94% (95% confidence interval: 89, 98) and 98% (95% confidence interval: 95, 100). In these groups, vaccine effectiveness was comparably high. Early two-dose measles vaccination is associated with improved coverage and a comparably high level of humoral immunity and clinical protection as a single dose at age > or =12 months. This strategy can be useful in areas at high risk for measles among infants.

The assessment of potential "breakthrough infections" in HIV vaccine trials requires knowledge of viral load in unvaccinated persons. Therefore, HIV-1 RNA was quantitated in plasma from Thai adults with subtype E infections. RNA was detectable (> or =500 copies/ml) in 93% of 255 specimens, with a mean (standard deviation) value of 4.09 (0.88) log copies/ml. The concentration of RNA was directly related to the presence of AIDS-defining illnesses, inversely related to CD4 count, and independent of gender after adjustment for CD4 count.

A study was carried out in Thailand to determine the frequency of reactivity to delayed-type hypersensitivity (DTH) skin tests used for the staging of HIV patients in the United States. A four-antigen panel which included tetanus toxoid (1:10), Candida (1:10), mumps and Trichophyton antigens was assessed in 221 adult subjects from across the full immunological spectrum of HIV disease. Complete anergy was found in 38 per cent of 73 subjects with CD4 counts of 0-200 cells/ml and in 6 per cent of 78 subjects with 201-400 cells/ml. Partial anergy (response to 1 of 4 antigens) was found in 26 per cent of the 0-200 cell/ml group and decreased progressively with increasing CD4 cell count. Results suggested that a 3-member recall antigen panel would provide nearly all the clinically useful information gained by the more standard 4-member panel. In conclusion, DTH skin testing was confirmed to provide a method of assessing the integrity of cellular immune function of HIV-infected Thai adults which correlated with disease progression.

Background. Women born in the United States after measles vaccine licensure in 1963 transfer less measles antibody to their infants than do older women. This may result in increased susceptibility to measles among infants. Objective. To determine the effect of maternal year of birth on the risk for measles in infants. Methods. We enrolled 128 unvaccinated infants ≤15 months of age who had documented exposure to measles from 1990 through 1992 in a retrospective cohort study. We interviewed their mothers by telephone to obtain demographic data, medical and vaccination history, and details of measles exposure and outcome. We used logistic regression analysis to estimate the effect of maternal year of birth. Results. Infants whose mothers were born after 1963 had a measles attack rate of 33%, compared with 12% for infants of older mothers. In logistic regression analysis, the adjusted odds ratio for maternal year of birth (born after 1963) was 7.5 (95% confidence interval 1.8, 30.6). Other significant risk factors were older infant age, mothers who developed measles after delivery, and exposure within 2 days of the rash onset of the exposing case. Conclusions. Infants whose mothers were born after 1963 are more susceptible to measles than are infants of older mothers. An increasing proportion of infants born in the United States may be susceptible to measles. Infants at high risk of exposure to measles should be vaccinated at 12 months of age. Vaccination programs that reduce transmission of the measles virus in the general population reduce the risk of infant exposure to measles.

A globally effective vaccine will need to elicit cytotoxic T lymphocytes (CTL) capable of recognizing diverse human immunodeficiency virus type 1 (HIV-1) clades. Study of the cellular immune responses of HIV-1—infected persons may allow predictions to be made regarding useful vaccine antigen components. The frequency and magnitude of CTL responses to clade E and B Gag, Pol-RT, Env, and Nef proteins were compared in 12 HLA-characterized, clade E—infected Thais and in 10 clade B—infected North Americans using vaccinia recombinant constructs for protein expression. While responses were detected against all proteins, they were most frequent and cross-reactive to Gag in both groups. Pol-RT was recognized less frequently in Thais than North Americans. Cross-clade protein recognition was common but not uniformly present among these HLA-disparate individuals. Population-specific CTL data are needed to adequately prepare for vaccine trials outside of North America and Europe.

Vaccine efficacy and mortality in successive cohorts of children who routinely received either Edmonston-Zagreb high-titre (EZ-HT) or Schwarz standard (SW-STD) measles vaccines have been examined in a rural area of Senegal. The 2 vaccines were equally protective against measles infection (vaccination efficacy: EZ-HT 94%; SW-STD 93%). Children who did not attend a scheduled session to receive measles vaccine had a higher mortality rate between 9 months and 2 years of age than did children receiving either EZ-HT (mortality ratio [MR] = 1 · 81, 95% confidence interval [CI] 1 · 06–3 · 08) or SW-STD measles vaccine (MR = l · 74, 95% CI 0 · 95–3 · 21). Children of either sex vaccinated with EZ-HT had lower mortality than their equivalents who had not received any measles vaccine. There was no difference in overall mortality between recipients of EZ-HT and SW-STD (MR = 0 · 96,95% CI 0 · 70–1 · 30). Using a Cox regression analysis to adjust for sex, age and significant background factors (season and death of mother), mortality rates tended to be lower for male recipients of EZ-HT than for boys receiving SW-STD (MR = 0 · 73, 95% CI 0 · 50–1 · 11) and higher for girls receiving EZ-HT than for girls receiving SW-STD (MR = 1 · 30, 95% CI 0 · 81–2 · 09) (test of interaction between sex and vaccine, P = 0 · 067). The tendency to reduced survival benefit for girls following receipt of high-titre measles vaccines substantiated observations from randomized trials in Guinea-Bissau, Senegal and Haiti. Existing data provide little support for the notion that high-titre vaccine is deleterious but it may not have the same beneficial effects as standard-titre measles vaccine.

At 3-5 years of age, female recipients of Edmonston-Zagreb high-titre (EZ-HT) and Schwarz high-titre (SW-HT) measles vaccine had lower survival rates than female recipients of Schwarz standard measles vaccine (SW-STD) in Guinea-Bissau, Senegal and Haiti. In Senegal, the children who received high-titre vaccines have now been followed to the age of 5-7 years to determine whether the difference in mortality persisted, and whether differences in vaccine efficacy were apparent. At this age there was no difference in mortality between female recipients of high-titre and standard titre measles vaccines. There was no indication that high-titre EZ-HT vaccine at 5 months (EZ-HT,5m) provided suboptimal protection, as vaccine efficacy after exposure was 97% and 95%, respectively, for EZ-HT,5m and SW-STD,10m vaccines, whereas SW-HT,5m vaccine had an efficacy of 81%. The difference in mortality between recipients of high-titre vaccines and SW-STD observed in several studies during the first few years after vaccination may be explained by non-specific beneficial effects of the standard measles vaccine rather than a harmful effect of the high-titre vaccines.

BACKGROUND:During 1989 and 1990 reported measles cases in the United States increased 6- to 9-fold over the annual mean of 3000 between 1985 and 1988. To evaluate recent epidemiology we summarized measles outbreaks. METHODS:Confirmed measles cases reported to the National Notifiable Disease Surveillance System during 1987 through 1990 were analyzed. An outbreak was defined as > or = 5 epidemiologically linked cases. RESULTS:There were 815 outbreaks, accounting for 94% of the 52,846 cases reported. Similar to 1985 and 1986, 3 patterns of measles transmission during outbreaks were identified: (1) predominantly among unvaccinated pre-school age children < 5 years of age (38% of outbreaks); (2) predominantly among vaccinated school age children 5 to 17 years of age (40%); and (3) predominantly among unvaccinated and vaccinated post-school age persons > or = 18 years of age (22%). Most outbreaks were small (median, 12 cases), but very large outbreaks occurred (maximum size, 10,670). Although school age outbreaks (58%) predominated during 1987 and 1988, preschool age (40%) and post-school age (23%) outbreaks were more important during 1989 and 1990. CONCLUSIONS:Recent epidemiology suggests that to achieve elimination of measles, ACIP recommendations must be fully implemented, including (1) routine administration of the first dose of measles vaccine from 12 to 15 months of age and (2) use of a routine two-dose schedule to prevent school age and post-school age outbreaks.

During a measles vaccine trial in a rural area of Senegal, antibody status was examined within 10 days of exposure for 228 previously vaccinated and 313 unvaccinated children more than 12 months old who were exposed to measles at home. Thirty-six percent of the children developed clinical measles, the clinical diagnosis being confirmed for 135 of the 137 children from whom 2 blood samples were collected. Vaccine efficacy was 90% (95% confidence interval, 83 to 94%). The hemagglutinin-inhibiting antibodies (HI) or plaque neutralizing antibodies (PN) assays were equally efficient in predicting susceptibility and protection against measles. Vaccinated children who had no detectable HI or PN antibodies at exposure had significant protection against measles compared with seronegative unvaccinated children (HI vaccine efficacy, 49% (95% confidence interval, 21 to 68%); PN vaccine efficacy, 43% (95% confidence interval, 12 to 62%)). The attack rate was high for children with a titer of 40 to 125 mIU) 67% (4 of 6) of those with a positive hemagglutinin-inhibiting antibody test and 36% (13 of 36) of those with a positive PN test developed measles. Attack rates among children with HI or PN titers above 125 mIU were 2% (6 of 295) and 3% (7 of 258), respectively. Because titers of ≥120 mIU have been found to offer little protection in another study, this antibody level may be the best screening value for assessing susceptibility and protection against measles. However, it should be noted that many seronegative vaccinated children are protected against measles infection.

Colleagues-In measles vaccine trials in Guinea-Bissau [I], Senegal [2], and Haiti [3], girls who received high-titer Edmonston-Zagreb (EZ; > lo4-' infectious particles) or Schwarz measles vaccines at 4-6 months of age had a higher mortality than girls receiving standard measles vaccine at 9-10 months of age. An explanation of this surprising observation, which was not due to insufficient protection against measles [2,4, 51, is important for the future development of measles vaccines and measles control. We and others [3] thought that high-titer measles vaccine could mimic natural measles, inducing immunosuppression with subsequent susceptibility to other infections. Thus, like others in Guinea-Bissau [6] and Peru [7], we undertook an immunologic examination ofa subsample of 143 children who had received high-titer EZ or standard-titer Schwarz measles vaccines. Little is known about the best predictors of immunocompetence among children in developing countries, so we used several different tests with the objectives of finding immunologic differences between the vaccine groups and identifying possible defects that could be corrected through specific interventions (e.g., vitamin A supplementation or nutritional rehabilitation). The study was camed out in Niakhar, Senegal, a rural area with a population of -26,000 [2]. The trial ofhigh-titer vaccine included all children bom to resident mothers between February 1987 and January 1989 [2]. There were 73 children who had received EZ vaccine at 5 months and 70 children who had received placebo at 5 months and standard Schwarz vaccine at 1 O months who were selected at random from the children residing in the study area in the fall of 1991 when the children were 36-44 months old. The children were visited at home three times. At the first visit, the children were examined anthropometrically, had a venous blood sample collected, and were vaccinated with diploid rabies vaccine lot El227 (Institut Mérieux, Lyon, France). Rabies vaccine was selected as a potentially beneficial immunization that none of the participants were likely to 4..

Administration of high-titre measles vaccine (Edmonston-Zagreb (EZ) at > 10(5) plaque-forming units (PFU) per dose) before the age of 9 months has been recommended in areas with high measles mortality before the routine age of immunization after 9 months. The study compares the long-term survival after high-titre measles immunization at 5 months of age with that following routine immunization with standard-titre vaccine at 10 months of age. At 5 months of age the high-titre group received Edmonston-Zagreb (EZ-HT, 5 months) or Schwarz (SW-HT, 5 months) at titres > 10(5) PFU per dose, while the standard-titre group received placebo at 5 months of age and < 10(4) PFU per dose of Schwarz vaccine at 10 months (SW-std, 10 months). All the children were followed up to at least 36 months of age. The mortality ratio (MR) for infants in the EZ-HT, 5 months and SW-HT, 5 months groups was 1.32 (P = 0.089) and 1.45 (P = 0.092), respectively, which did not differ significantly from that of recipients of the SW-std, 10 months. The higher MR among recipients of the high-titre vaccines was due to the significantly lower survival among females compared with the females who received SW-std vaccine (EZ-HT, 5 months MR = 1.76, P = 0.013; SW-HT, 5 months MR = 2.14, P = 0.017). For children aged 5-10 months the high-titre measles vaccine did not increase mortality relative to unvaccinated children who had received placebo.

The appropriate age for measles vaccination is determined by weighing the risk of measles disease and complications at a given age with vaccine efficacy at that age. In the United States, measles vaccine was initially used in children as young as 9 months of age because the disease was common and complications were greatest in persons less than 1 year of age. In 1965, when it became apparent that vaccine failure was unacceptably high in children less than 1 year and when epidemiologic analysis indicated that children greater than or equal to 1 year, particularly schoolchildren, were the primary focus of measles transmission, the vaccination age was raised to 12 months. In 1976, further studies showed efficacy was slightly higher at 15 months of age versus 12 months or 12-14 months of age. Because the risk of acquiring measles in children less than 15 months was low, the age for routine vaccination was increased to 15 months. This age recommendation may be appropriate for developed countries where the epidemiology of measles may be similar to the epidemiology in the United States. However, this age is inappropriate for many countries in the developing world where the risks of measles and complications from measles are high in young preschool children. In those countries, the recommended age for routine vaccination against measles is generally 9 months.

Three patients with known or subsequently proven sarcoidosis had CT of the retroperitoneum because of clinical symptoms referable to this area. Gross splenomegaly was evident in all cases. The liver was massively enlarged in one patient and normal size in two patients. Lymphadenopathy was present in many nodal groups.